The role of renal hypoxia in the pathogenesis of diabetic kidney disease: a promising target for newer renoprotective agents including SGLT2 inhibitors?
Open accessAbstract
Diabetic kidney disease is the most common cause of end-stage kidney disease and poses a major global health problem. Finding new, safe, and effective strategies to halt this disease has proven to be challenging. In part that is because the underlying mechanisms are complex and not fully understood. However, in recent years, evidence has accumulated suggesting that chronic hypoxia may be the primary pathophysiological pathway driving diabetic kidney disease and chronic kidney disease of other etiologies and was called the chronic hypoxia hypothesis. Hypoxia is the result of a mismatch between oxygen delivery and oxygen demand. The primary determinant of oxygen delivery is renal perfusion (blood flow per tissue mass), whereas the main driver of oxygen demand is active sodium reabsorption. Diabetes mellitus is thought to compromise the oxygen balance by impairing oxygen delivery owing to hyperglycemia-associated microvascular damage and exacerbate oxygen demand owing to increased sodium reabsorption as a result of sodium-glucose cotransporter upregulation and glomerular hyperfiltration. The resultant hypoxic injury creates a vicious cycle of capillary damage, inflammation, deposition of the extracellular matrix, and, ultimately, fibrosis and nephron loss. This review will frame the role of chronic hypoxia in the pathogenesis of diabetic kidney disease and its prospect as a promising therapeutic target. We will outline the cellular mechanisms of hypoxia and evidence for renal hypoxia in animal and human studies. In addition, we will highlight the promise of newer imaging modalities including blood oxygenation level-dependent magnetic resonance imaging and discuss salutary interventions such as sodium-glucose cotransporter 2 inhibition that (may) protect the kidney through amelioration of renal hypoxia.
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Kidney hypoxia may be driven by impaired oxygen delivery resulting from microvascular damage and by increased oxygen consumption caused by glomerular hyperfiltration and inefficient energy generation due to impaired insulin sensitivity.
“First, it may be due to impaired oxygen delivery resulting from microvascular damage. Second, increased oxygen consumption, caused by both glomerular hyperfiltration and inefficient energy generation due to impaired insulin sensitivity, may also contribute (38).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [38]
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Self-citationRole of Renal Oxygenation and Mitochondrial Function in the Pathophysiology of Acute Kidney Injury
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Diffusion of oxygen from arterial to venous segments of renal capillaries
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Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation
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Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice
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Self-citationRenal tubular Na(+)-K(+)-ATPase in diabetes mellitus: relationship to metabolic abnormality
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Self-citationModeling glucose metabolism and lactate production in the kidney
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Renal Hypoxia: An Important Prognostic Marker in Patients with Chronic Kidney Disease
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Intrarenal red cell and plasma volumes in the non-diuretic rat
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Hypoxia and hypoxia-inducible factors in chronic kidney disease
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Self-citationEndogenous vasopressin regulates Na-K-ATPase and Na+-K+-Cl−cotransporterrbsc-1in rat outer medulla
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Diabetic vascular diseases: molecular mechanisms and therapeutic strategies
Li, Y., Liu, Y., Liu, S., Gao, M., Wang, W., Chen, K., Huang, L., & Liu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01400-z · Cited by 763 · see citing works
Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2
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An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors
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Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients
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Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment
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Update on diagnosis, pathophysiology, and management of diabetic kidney disease
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“increase energy consumption of tubular cells as a result of upregulated sodium-glucose cotransport and glomerular hyperfiltration.(36) Oxidative stress-induced mitochondrial uncoupling further increases oxygen demand.”
BackgroundCombination therapy for kidney disease in people with diabetes mellitus
van Raalte, D. H., Bjornstad, P., Cherney, D. Z. I., de Boer, I. H., Fioretto, P., Gordin, D., Persson, F., Rosas, S. E., Rossing, P., Schaub, J. A., et al. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00827-z · Cited by 127 · see citing works
Self-citationKim, M. N., Moon, J. H., & Cho, Y. M. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14503 · Cited by 110 · see citing works
Applications of SGLT2 inhibitors beyond glycaemic control
O’Hara, D. V., Lam, C. S. P., McMurray, J. J. V., Yi, T. W., HOCKING, S. L., Dawson, J., Raichand, S., Januszewski, A. S., & Jardine, M. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00836-y · Cited by 112 · see citing works
“By reducing the activity of SGLT2, and hence of Na + /K + ATPase, as well as the activity of NHE3, SGLT2 inhibition may reduce energy and oxygen consumption in the proximal convoluted tubule, enabling tubulointerstitial cells to better tolerate ischaemic or hypovolaemic events 31,40 .”
Up-Date on Diabetic Nephropathy
Pelle, M. C., Provenzano, M., Busutti, M., Porcu, C. V., Zaffina, I., Stanga, L., & Arturi, F. (2022) · Life · doi:10.3390/life12081202 · Cited by 110 · see citing works
SGLT2 inhibitor counteracts NLRP3 inflammasome via tubular metabolite itaconate in fibrosis kidney
Ke, Q., Shi, C., Lv, Y., Wang, L., Luo, J., Jiang, L., Yang, J., & Zhou, Y. (2021) · The FASEB Journal · doi:10.1096/fj.202100909rr · Cited by 86 · see citing works
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“Hypoxia is another important factor in the development of tissue stress in the kidneys, as it triggers a vicious cycle of capillary injury, inflammation, extracellular matrix deposition, and, eventually, fibrosis and nephron loss [27,103].”
BackgroundRenal blood flow and oxygenation
Edwards, A., & Kurtcuoglu, V. (2022) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-022-02690-y · Cited by 85 · see citing works
Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets
Zoja, C., Xinaris, C., & Macconi, D. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.586892 · Cited by 82 · see citing works
“Chronic hypoxia has been recognized as an important signaling pathway driving diabetic kidney disease (Hesp et al., 2020).”
BackgroundRole of oxidative stress in diabetes-induced complications and their management with antioxidants
Singh, H. B., Singh, R., Singh, A., Singh, H., Singh, G., Kaur, S., & Singh, B. (2023) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2023.2243651 · Cited by 83 · see citing works
“Diabetes and hyperglycaemia increase the energy consumption of tubular cells as a result of upregulated sodium-glucose co-transport and glomerular hyperfiltration (Hesp et al. 2020).”
Gullaksen, S., Vernstrøm, L., Sørensen, S. S., Ringgaard, S., Laustsen, C., Funck, K. L., Poulsen, P. L., & Laugesen, E. (2023) · Diabetologia · doi:10.1007/s00125-023-05876-w · Cited by 75 · see citing works
Yan, L. (2022) · Biomolecules · doi:10.3390/biom12091225 · Cited by 67 · see citing works
The complex pathology of diabetic nephropathy in humans
Kriz, W., Löwen, J., & Gröne, H. (2023) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfad052 · Cited by 70 · see citing works
“These data stand in stark contrast to hypotheses claiming that the damaging processes in DN may also start from a primary tubular injury initiated by the metabolic situation [48] or by local hypoxia [49].”
Langewisch, E. D., & Mannon, R. B. (2021) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.15590920 · Cited by 65 · see citing works
“These agents demonstrate renoprotective effects in native kidneys (68) and may have relevance to improved longterm kidney function in transplantation as well.”
BackgroundChae, S. Y., Kim, Y., & Park, C. W. (2023) · Antioxidants · doi:10.3390/antiox12122083 · Cited by 63 · see citing works
“…of mitochondrial oxidative phosphorylation in ATP synthesis, this can be detrimental to ATP production. oxygen demand of the kidneys increases by 50% to 100% [83]. generation during DKD [72] (Figure 3), exacerbating hypoxic injury, ultimately promoting the progression of the disease [80].”
BackgroundInfluentialTGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases
Tang, P. C., Chan, A. S.-W., Zhang, C.-B., Córdoba, C. A. G., Zhang, Y., To, K., Leung, K. T., Lan, H.-Y., & Tang, P. M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.628519 · Cited by 58 · see citing works
“CKD can be a primary disease or a complication initiated by other disorders, including glomerulonephritis (3), hypertension (4), diabetes (5), infection (6), and genetic causes (7).”
BackgroundHofherr, A., Williams, J. H., Gan, L., Söderberg, M. P., Hansen, P., & Woollard, K. J. (2022) · BMC Nephrology · doi:10.1186/s12882-022-02794-8 · Cited by 60 · see citing works
SGLT2 Inhibitors: The Sweet Success for Kidneys
Dharia, A., Khan, A. A., Sridhar, V. S., & Cherney, D. Z. I. (2023) · Annual Review of Medicine · doi:10.1146/annurev-med-042921-102135 · Cited by 61 · see citing works
Chen, J., Tang, T., Cao, J.-Y., Li, Z., Zhong, X., Wen, Y., Shen, A., Liu, B., & Lv, L. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.08.013 · Cited by 57 · see citing works
“Renal hypoxia that occurs in many types of kidney injury contributes to the development of TII, 26,27 but the underling mechanism has yet to be determined.”
Lu, Y.-P., Zhang, Z., Wu, H., Fang, L.-J., Hu, B., Tang, C., Zhang, Y., Yin, L., Tang, D., Zheng, Z., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03629-8 · Cited by 57 · see citing works
“Furthermore, SGLT2 inhibitors downregulate hepcidin and promote erythropoiesis [15, 16], thereby alleviating renal hypoxia by improving the circulating oxygen supply [7].”
BackgroundGlycolytic lactate in diabetic kidney disease
Darshi, M., Kugathasan, L., Maity, S., Sridhar, V. S., Fernandez, R. A., Limonte, C. P., Grajeda, B. I., Saliba, A., Zhang, G., Drel, V. R., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.168825 · Cited by 59 · see citing works
Self-citationCherney, D. Z. I., Udell, J. A., & Drucker, D. J. (2021) · Med · doi:10.1016/j.medj.2021.10.004 · Cited by 52 · see citing works
Liu, H., Sridhar, V. S., Lovblom, L. E., Lytvyn, Y., Burger, D. E., Burns, K. D., Brinc, D., Lawler, P. R., & Cherney, D. Z. I. (2021) · Kidney International Reports · doi:10.1016/j.ekir.2021.05.022 · Cited by 46 · see citing works
“In the setting of diabetes, energy-intensive sodium and glucose reabsorption in the proximal tubule is elevated, leading to renal hypoxia, generation of reactive oxygen species, and a proinflammatory milieu, which have been implicated in the progression of DKD and cardiovascular disease.(8) Accordingly, the reduction…”
BackgroundMetabolic reprogramming: A novel therapeutic target in diabetic kidney disease
Wang, M., Pang, Y., Guo, Y., Tian, L., Liu, Y., Shen, C., Liu, M., Meng, Y., Cai, Z., Wang, Y., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.970601 · Cited by 46 · see citing works
“These inhibitors reduced tubular reabsorption of glucose, thus lowering blood glucose and enhancing renal oxygenation of the cortical region (Hesp et al., 2020).”
BackgroundNephroprotection by SGLT2 Inhibition: Back to the Future?
Nicola, L. D., Gabbai, F. B., Garofalo, C., Conte, G., & Minutolo, R. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072243 · Cited by 41 · see citing works
The Forgotten Antiproteinuric Properties of Diuretics
Trujillo, H., Caravaca‐Fontán, F., Caro, J., Morales, E., & Praga, M. (2021) · American Journal of Nephrology · doi:10.1159/000517020 · Cited by 41 · see citing works
Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism
Narongkiatikhun, P., Choi, Y. J., Hampson, H. E., Gotzamanis, J., Zhang, G., van Raalte, D. H., de Boer, I. H., Nelson, R. G., Tommerdahl, K. L., McCown, P. J., et al. (2024) · Kidney International Reports · doi:10.1016/j.ekir.2024.09.019 · Cited by 42 · see citing works
Self-citationPrasad, P. V., Li, L., Hack, B. K., Leloudas, N., & Sprague, S. M. (2023) · Kidney International Reports · doi:10.1016/j.ekir.2023.02.1092 · Cited by 39 · see citing works
“Overall, qBOLD MRI allows for direct evaluation of kidney oxygen status and therefore facilitates mechanistic evaluation of interventions targeting kidney hypoxia such as sodium glucose cotransporter inhibitors.(60) The method as described can be translated to the clinic, however it may require further studies with a…”
MethodSelf-citationCPT1α maintains phenotype of tubules via mitochondrial respiration during kidney injury and repair
Yuan, Q., Lv, Y., Ding, H., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04085-w · Cited by 38 · see citing works
Iacobini, C., Vitale, M., Pugliese, G., & Menini, S. (2021) · Biomedicines · doi:10.3390/biomedicines9091139 · Cited by 34 · see citing works
Iordan, L., Gaiţă, L., Timar, R. Z., Avram, V. F., Sturza, A., & Timar, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137057 · Cited by 34 · see citing works
“The action of the latter two mechanisms inhibits essential pathways that lead to diabetic kidney injury and consecutively contributes to renoprotection for these patients [149,157–159].”
BackgroundHypoxia-Inducible Factors and Diabetic Kidney Disease—How Deep Can We Go?
Stăniguț, A. M., Pana, C., Enciu, M., Deacu, M., Cîmpineanu, B., & Tuta, L. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810413 · Cited by 34 · see citing works
Snel, L. I. P., Oosterom-Eijmael, M. J. P., Rampanelli, E., Lankadeva, Y. R., Plummer, M. P., Preckel, B., Hermanides, J., van Raalte, D. H., & Hulst, A. H. (2025) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2025.111811 · Cited by 32 · see citing works
Furth, S. L., Colhoun, H. M., Kanbay, M., Kukla, A., Lim, L., MacLaughlin, H. L., Navaneethan, S. D., Shroff, R. C., Stenvinkel, P., Cheung, M., et al. (2025) · Kidney International · doi:10.1016/j.kint.2025.09.019 · Cited by 40 · see citing works
Hare, G. M. T., Zhang, Y., Chin, K., Thai, K., Jacobs, E., Cazorla‐Bak, M. P., Nghiem, L., Wilson, D. F., Vinogradov, S. A., Connelly, K. A., et al. (2021) · Physiological Reports · doi:10.14814/phy2.14890 · Cited by 31 · see citing works
“| 3 of 16HARE Et Al. delivery by increasing afferent arteriolar tone through tubuloglomerular feedback (TGF; Hesp et al., 2020) and potentially decrease efferent arterial flow; thereby reducing postglomerular perfusion to the tubular network (Lytvyn et al., 2017).”
BackgroundInfluentialSGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation
Klen, J., & Dolžan, V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071995 · Cited by 30 · see citing works
“SGLT2 inhibitors may also attenuate kidney hypoxia by reducing the energy expenditure involved in tubular sodium and glucose reabsorption, leading to increases in erythropoietin production and hematopoiesis [49,52,53].”
BackgroundMitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications
Afşar, B., Hornum, M., Afşar, R. E., Ertuğlu, L. A., Ortíz, A., Covic, A. C., van Raalte, D. H., Cherney, D. Z. I., & Kanbay, M. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.02.016 · Cited by 28 · see citing works
Mora‐Gutiérrez, J. M., Fernández‐Seara, M. A., Echeverría‐Chasco, R., & Garcı́a-Fernández, N. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112461 · Cited by 29 · see citing works
Nephroprotective Properties of Antidiabetic Drugs
Gerdes, C., Muller, N., Wolf, G., & Busch, M. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12103377 · Cited by 29 · see citing works
The Pathophysiological Basis of Diabetic Kidney Protection by Inhibition of SGLT2 and SGLT1
Oe, Y., & Vallon, V. (2022) · Kidney and Dialysis · doi:10.3390/kidneydial2020032 · Cited by 28 · see citing works
Self-citationZhou, S., Zhang, Y., Wang, T., Huang, S., Gong, S., Wang, J., & Yu, P. (2021) · Diabetes & Metabolism · doi:10.1016/j.diabet.2021.101274 · Cited by 26 · see citing works
Afşar, B., & Afşar, R. E. (2022) · Pharmacological Reports · doi:10.1007/s43440-022-00442-4 · Cited by 28 · see citing works
“Indeed, it was suggested that the protective effect of HIF on the kidney occurs in AKI, but long-term permanent activation may be detrimental resulting in chronic inflammation, fibrosis, and extracellular matrix accumulation [32].”
BackgroundSex and Gender Related Differences in Diabetic Kidney Disease
Sridhar, V. S., Yau, K., Benham, J. L., Campbell, D. J. T., & Cherney, D. Z. I. (2022) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2022.04.007 · Cited by 23 · see citing works
Wang, R., Lin, Z., Yang, X., Zhao, K., Wang, S., Sui, X., Su, T., & Wang, X. (2021) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.27814 · Cited by 23 · see citing works
“In the early phase of DKD, the upregulation of SGLTs and enhanced sodium-glucose cotransport increase the proximal tubular reabsorption of sodium chloride and fluid.(4) The activity of the Na-K–ATPase pump is highest in the proximal tubule and in the thick ascending limb of the loop of Henle, located in the OS.”
BackgroundInfluentialSørensen, S. S., Gullaksen, S., Vernstrøm, L., Ringgaard, S., Laustsen, C., Funck, K. L., Laugesen, E., & Poulsen, P. L. (2022) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfac186 · Cited by 22 · see citing works
Cardiorenal Protection in Diabetic Kidney Disease
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“Diabetic chronic kidney disease is characterized by tissue hypoxia [116], oxidative [117] and endoplasmic reticulum stress [118], and an altered and inadequate autophagic response to cellular stress [119] that lead to activation of HIF-1α and inhibition of HIF-2α.”
BackgroundNext-generation therapeutics for diabetic kidney disease
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“It remains to be determined how GLP-1 confers its kidney benefits, as the only GLP-1 receptor that has been identified has limited expression in the kidney (8).”
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“Indeed, this reabsorption is dependent on the electrochemical gradient of sodium established by the Na/K co-transporter, consuming adenosine triphosphate generated by oxidation [83].”
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“Elevated blood glucose levels in type 2 diabetes (T2D) patients can cause serious, even catastrophic, vascular consequences such as amputations, atherosclerosis, retinopathy, neuropathy, and nephropathy [2,3].”
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“29 31 – 33 Hypoxia, in turn, triggers in fl ammatory responses that induce the development of renal fi brosis.”
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“This releases more MPs and inflammatory mediators, resulting in a vicious cycle and exacerbating thrombosis and kidney injury (Hesp et al., 2020; Dadson et al., 2020).”
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Attenuated kidney oxidative metabolism in young adults with type 1 diabetes
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Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming
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Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes
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“36, 50 MRI offers non-invasive non-invasive full coverage of the kidney, and the MRI relaxation times T 2 *, T 2 appear to”
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“Apart from the activation of the TGF, other mechanisms for the beneficial effects of SGLT2i on kidney function have been proposed (Table 1): induction of ketone body production and an elevation in hematocrit concentration, which can contribute to the beneficial effect of these agents on cardiovascular outcomes [30]; l…”
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“Adding an SGLT2i may decrease hypoxia-inducible factor-1alpha (HIF-1alpha) in the kidney, revealing less tissue hypoxia [57].”
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Sodium-glucose cotransporter 2 inhibitors as the first universal treatment of chronic kidney disease
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“Inhibition of proximal tubular glucose and sodium re-absorption is also thought to have favourable effects on renal energetics, with subsequent effects on hypoxia, inflammation, and fibrosis [24 , 25 ].”
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New Approaches to Diabetic Nephropathy from Bed to Bench
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“In addition, up-regulation of sodium-glucose cotransporter-2 and glomerular ultra fi ltration in diabetic patients leads to increased oxygen consumption due to sodium reabsorption, resulting in renal hypoxia and fi brosis [34].”
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More reasons to use SGLT2 inhibitors: EMPEROR-reduced and DAPA-CKD
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Pathophysiology of Diabetic Kidney Disease
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- Authors
- Hesp, A. C., Schaub, J. A., Prasad, P. V., Vallon, V., Laverman, G. D., Bjornstad, P., & van Raalte, D. H.
- Affiliations
- Amsterdam University Medical Centers (NL)
- University of Michigan (US)
- Endeavor Health (US)
- University of California San Diego (US)
- Ziekenhuis Groep Twente (NL)
- University of Colorado Anschutz (US)
- Corresponding author
- Hesp, Anne C.
- ORCID
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 98
- Issue
- 3
- Pages
- 579-589
- ISSN
- 0085-2538 (ISSN-L)
- PMC
- PMC8397597
- OpenAlex
- W3020088156
- Cited by
- 202
- References
- 120
- Citations by year
- 2026: 30 · 2025: 34 · 2024: 25 · 2023: 38 · 2022: 40 · 2021: 32 · 2020: 3
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK106557)
- National Institutes of Health (R01DK112042, R01DK106102, R01HL142814, RF1AG061296)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- diabetic nephropathy, renal hypoxia, oxygen delivery, oxygen requirement, sodium-glucose cotransporter 2 inhibition, SGLT2 inhibitors, renal perfusion, glomerular hyperfiltration, sodium reabsorption, renal fibrosis, extracellular matrix deposition, BOLD MRI, renal protection, end-stage renal disease
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Hypoxia, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Humans, Hyperglycemia, Hypoglycemic Agents, Kidney
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